ABSTRACT Trauma or infection that results in segmental bone loss poses a common, difficult reconstruction dilemma for orthopedic surgeons. Devascularized bone does not heal and is prone to infection. Clinically, it is well established that both an angiogenic and osteogenic environment is needed, but traditionally these two processes have been studied in isolation. This has resulted in many treatment options, but no one solution that works in every patient. Human placental tissue has been shown to have both angiogenic and osteogenic capabilities. It is unknown if these properties can successfully augment the mineralization of critical-sized bone defects. Purified human placental-derived matrix (hPM) is rich in growth factors and has been shown to rapidly create morphologically and phenotypically accurate vascular structures in vitro and functional vessels in vivo. We hypothesize that hPM can facilitate angiogenesis on demineralized bone graft, thus enhancing mineralization of defects. We will measure the angiogenic and osteogenic response to hPM in vitro in 3D culture and test healing of a critical sized defect in an in vivo rat femur defect model.